Repeat traumatic brain injury exacerbates acute thalamic hyperconnectivity in humans

Abstract

Abstract Repeated mild traumatic brain injury (mTBI) is of growing interest regarding public and sporting safety and is thought to have greater adverse or cumulative neurological effects when compared with single injury. While epidemiological links between repeated TBI and outcome have been investigated in humans, exploration of its mechanistic substrates have been largely undertaken in animal models. We compared acute neurological effects of repeat mTBI (n=21) to that of single injury (n=21) and healthy controls (n=76) using resting-state functional magnetic resonance imaging, and quantified thalamic functional connectivity, given previous identification of its prognostic potential in human mTBI and rodent repeat mTBI. Acute thalamocortical functional connectivity showed a rank-based trend of increasing connectivity with number of injuries, at local and global scales of investigation. Thus, history of as few as two previous injuries can induce a vulnerable neural environment of exacerbated hyperconnectivity, in otherwise healthy individuals from non-specialist populations. These results further establish thalamocortical functional connectivity as a scalable marker of acute injury and long-term neural dysfunction following mTBI.